‘Men have changed’: Growing interest in male contraception sparks transdermal gel research

Key takeaways:

• A transdermal gel for men was effective in blocking sperm production in a phase 2 study.
• More men have expressed interest in availability of male contraceptive options since the Dobbs decision.

Growing interest in male contraceptive options in the wake of the Dobbs decision and current abortion laws have spurred increased attention in development of a transdermal gel for men to block sperm production.

“We are really working for gender equity. Men and women need to have choices at different times of the reproductive life, whether they are young adolescents or mature couples with the need to postpone or space pregnancy or when they complete their family and want a long-acting or nonreversible method,” Regine Sitruk-Ware, MD, distinguished scientist at the Center for Biomedical Research at the Population Council in New York, told Healio. “We need to have several methods available so they can choose.”

Sitruk-Ware and colleagues conducted a review, published in Contraception, evaluating reversible contraceptive methods for men and the importance of a novel, cost-effective male contraceptive option to reduce global unintended pregnancy rates.

Healio spoke with Sitruk-Ware about reversible contraceptive methods for men, how they work and the implications of an approved transdermal gel for male contraception.

Healio: What reversible contraceptive methods are currently available for men?

Sitruk-Ware: Not many. They have only the condom and vasectomy. I don’t think we can call withdrawal a real method. It’s used, but it’s also prone to failure. Condom and withdrawal failure rates are approximately 13%. There is research underway for vasectomy reversibility, but at this stage, vasectomy is not reversible. It is only recently that there has been more interest in developing male contraceptives. At the Population Council, we have been working a long time for gender equity and trying to develop methods both for men and women.

We conducted a phase 2b project, which is a large efficacy and safety study, in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development for transdermal gel (Nestorone plus testosterone [NES/T]), that is the most advanced method, that has just completed.

Healio: Why did it take so long for research on male contraception to advance?

Sitruk-Ware: For many years, the industry, and even men themselves, didn’t think that a new contraceptive method would be of interest. Many thought it was the woman’s responsibility. Now, fortunately, men have changed, and they are asking for shared responsibility in the choices of a method, in discussion with their partner. At the beginning of 2005, there was a large survey conducted at the request of Schering AG, which was at that time a company interested in male contraception. Interestingly, about 55% of men reported being ready to use a new contraceptive method, including about 45% of U.S. men. But in the industry, only two medium-sized companies were interested at the time they started a common program of male hormonal contraception. Unfortunately, they were acquired by bigger pharmaceutical companies and the project disappeared.

A recent survey of 12,435 men commissioned by the Gates Foundation and the Male Contraception Initiative showed that almost 80% of respondents would be interested in a male contraceptive method at some point in time. On average, 61% of men showed interest in trying novel male contraceptives in their first year of availability, ranging from 39% before and 49% after Dobbs in the U.S. to 76% in Nigeria and Bangladesh.

We saw this interest when we initiated and conducted the phase 2b study of the transdermal gel. Women trusted their partner to use the gel, men were very keen to use the gel and they wanted to reenroll when they finished 1 year of treatment. We also see more interest from small companies that have now entered this field. One company, Contraline, is developing a hydrogel for reversible vasectomy, and Your Choice Therapeutics is developing a product that acts on maturation of sperm. These two are in phase 1 studies in the clinic. Sacyl Pharma is working on an oral tablet for on-demand contraception for men, but this is still in animal studies. We are confident for the future because we have seen good results and so much interest from the participants that I think we can plan for a phase 3 study next year.

Healio: Could you explain what the male contraceptive transdermal gel is and how it works?

Sitruk-Ware: The transdermal gel is a clear, nongreasy gel that dries quickly after application. There is a higher concentration of two hormones in this gel. One is Nestorone (segesterone acetate), which is a progestin developed at the Population Council for female contraception. It was approved by the FDA in 2018 in a contraceptive vaginal system. Because Nestorone blocks the pituitary gland and the two hormones that orchestrate the production of sperm and the secretion of testosterone, there is no more sperm, but also no more testosterone. We have to replace testosterone at levels of replacement therapy. So, the gel is a combination of Nestorone and testosterone. We completed several dose finding studies and found the appropriate combination, which is Nestorone 8 mg and testosterone 74 mg, factoring in that when you apply a gel for any hormone, 10% is absorbed through the skin.

The gel is available in canisters with 30 doses for a month and the man has to activate the head of the canister and apply 2.5 g to one shoulder and another 2.5 g on the other shoulder. He would rub it gently and let it dry and then the product will be absorbed. The gel should be applied once a day for several weeks before it blocks sperm production. The area must be protected if he has sexual activity, so it does not transmit to his partner.

Healio: What do current studies on this transdermal gel show?

Sitruk-Ware: We had several previous studies where we demonstrated that we could achieve complete suppression of sperm and it is maintained and it is reversible. The advantage of the transdermal application is that you can obtain a retention of the product in the skin for 48 hours. So, if he forgets one day, there is no risk. If he forgets several days in a row, there is a risk of rebound of sperm production. We warn participants about this and we have been pleased to see how most men in the clinical trial have good compliance.

Healio: What are some of the barriers to approving a transdermal contraceptive gel for men?

Sitruk-Ware: For a long time, there was no new contraceptive for men because there were no guidelines by the FDA or the European agency to explain how to develop a male contraceptive. Every sponsor who wants to develop a product for female contraception knows what the FDA is expecting, but no such guidelines exist for male methods. We had several meetings with the FDA and have worked with them to establish some guidance on the first steps. We collected plenty of safety data in men. We are also preparing the results of this just completed study: the report, a full statistical analysis, a publication plan, and we are preparing the protocol for the phase 3 study.

The important next step is to find funding. Running a phase 3 program is very costly. At this stage, there are very few companies that are working in this field, apart from nonprofit organizations or government agencies, like NIH. We currently have granted an exclusive option agreement to license NES/T gel to the biotech company Contraline and they are in discussions with different investors to continue development and fund the phase 3 program. If that happens, we would probably see this product approved by the end of this decade.

For more information:

Regine Sitruk-Ware, MD, can be reached at rsitrukware@popcouncil.org; X (Twitter): @Pop_Council; LinkedIn: @Population Council; Facebook: @PopCouncil.

References:

• Kaur J, et al. Andrology. 2024;doi:10.1111/andr.13726.
• Sitruk-Ware R, et al. Contraception. 2025;doi:10.1016/j.contraception.2025.110830.